3 ms·

This is a hopeful but possible take. But the 501Y.V2 (B.1.351) and 501Y.V3 (P1) lineages have the mutation within the conserved region for coronaviruses near th

This is a hopeful but possible take. But the 501Y.V2 (B.1.351) and 501Y.V3 (P1) lineages have the mutation within the conserved region for coronaviruses near the spike protein cleavage site. These show massively (1000x) decreased monoclonal antibody binding for original genetic sequence designs. It's better for the mRNA vaccine produced human-body-made antibodies which show only 5-10x reduction in binding. But antibody binding isn't the full story and there may be T-cell stuff helping too. The data seems to indicate updated spike protein designs will be needed but if there's other stuff going on we don't know about old spike vaccines could still work. I can't say it will definitely help because the vaccine rollout is so slow and air travel is so fast that this negative pressure will probably provoke more variants as long as host numbers remain high. ref: "Antibody Resistance of SARS-CoV-2 Variants B.1.351 and B.1.1.7" [pdf] https://www.nature.com/articles/s41586-021-03398-2_reference.pdf https://www.nature.com/articles/s41586-021-03398-2_reference... https://i.imgur.com/8co1IoL.jpg https://i.imgur.com/8co1IoL.jpg "SARS-CoV-2 VoC B.1.1.7 and B.1.351 neutralization evasion" table. https://covariants.org/variants/S.501Y.V2 https://covariants.org/variants/S.501Y.V2 https://covariants.org/variants/S.501Y.V3 https://covariants.org/variants/S.501Y.V3

Pyramus 6y ago
Thank you for the references!
randomsearch 6y ago
How does a 5x reduction in binding actually impact infection?
- mlyle 6y ago
  The vaccines create a much more potent antibody response than the titers we see in convalescent plasma. 5-10x less binding probably translates to somewhat reduced efficacy (no one really knows, but 75% vs. 95% might be a reasonable guess). Of course, this is a really complicated thing, because it's not just the immediate antibody response, but also the T-cell response, and also how quickly on a subsequent infection the set of antibodies develops and broadens even more. We do know that e.g. in Israel where there's very high amounts of vaccine deployed and nasty variants, that case control studies show a large effect still.
hanklazard 6y ago
The monoclonal data is less concerning since the human antibody response is polyclonal. It’s not surprising that this virus can escape from a single targeted antibody and if I were in pharm, this is why I wouldn’t spend billions on a mAb drug. I agree that the decreased convalescent plasma effectiveness is not ideal but I doubt this virus will be able to fully escape the mRNA vaccines on a population level. Polyclonal antibodies against spike + t-cells + herd immunity should be enough to quell this pandemic. At least I hope so.
- abacadaba 6y ago
  The new one is supposed to be targeting a conserved site on the protein, where any change would make it non functional https://www.investorideas.com/news/2021/biotech/03122Vir-COVID-19-Trial.asp https://www.investorideas.com/news/2021/biotech/03122Vir-COV... "The company commented that compared with other monoclonal antibodies, "VIR-7831 binds to a highly conserved epitope of the spike protein, which may make it more difficult for resistance to develop." Vir Biotechnology's CEO George Scangos, Ph.D., commented, "These exciting data with a single antibody against a conserved epitope bring us one step closer to delivering an effective new solution to patients around the globe."
  - hanklazard 6y ago
    I guess I'm just skeptical that anyone can be truly sure of which exposed epitopes are conserved (I haven't seen data on this residue or drug, these are just my thoughts). Given that we're talking about a three dimensional structure, you really need a number of conserved residues in physical proximity to have an inescapable monoclonal antibody. It seems quite possible that there aren't any targets like this and that only a polyclonal immune response, or maybe a cocktail of monoclonals, can be effective in the long-term.

Pyramus 6y ago

Thank you for the references!

randomsearch 6y ago

How does a 5x reduction in binding actually impact infection?

mlyle 6y ago
The vaccines create a much more potent antibody response than the titers we see in convalescent plasma. 5-10x less binding probably translates to somewhat reduced efficacy (no one really knows, but 75% vs. 95% might be a reasonable guess). Of course, this is a really complicated thing, because it's not just the immediate antibody response, but also the T-cell response, and also how quickly on a subsequent infection the set of antibodies develops and broadens even more. We do know that e.g. in Israel where there's very high amounts of vaccine deployed and nasty variants, that case control studies show a large effect still.

hanklazard 6y ago

The monoclonal data is less concerning since the human antibody response is polyclonal. It’s not surprising that this virus can escape from a single targeted antibody and if I were in pharm, this is why I wouldn’t spend billions on a mAb drug. I agree that the decreased convalescent plasma effectiveness is not ideal but I doubt this virus will be able to fully escape the mRNA vaccines on a population level. Polyclonal antibodies against spike + t-cells + herd immunity should be enough to quell this pandemic. At least I hope so.

abacadaba 6y ago
The new one is supposed to be targeting a conserved site on the protein, where any change would make it non functional https://www.investorideas.com/news/2021/biotech/03122Vir-COVID-19-Trial.asp https://www.investorideas.com/news/2021/biotech/03122Vir-COV... "The company commented that compared with other monoclonal antibodies, "VIR-7831 binds to a highly conserved epitope of the spike protein, which may make it more difficult for resistance to develop." Vir Biotechnology's CEO George Scangos, Ph.D., commented, "These exciting data with a single antibody against a conserved epitope bring us one step closer to delivering an effective new solution to patients around the globe."
- hanklazard 6y ago
  I guess I'm just skeptical that anyone can be truly sure of which exposed epitopes are conserved (I haven't seen data on this residue or drug, these are just my thoughts). Given that we're talking about a three dimensional structure, you really need a number of conserved residues in physical proximity to have an inescapable monoclonal antibody. It seems quite possible that there aren't any targets like this and that only a polyclonal immune response, or maybe a cocktail of monoclonals, can be effective in the long-term.